The goal of this proposal is to develop a non-protein small molecule inhibitor of apoptosis found in normal human urine as a therapeutic to prevent radiation or chemotherapy-induced alopecia in cancer patients. Radiation treatment, as well as some chemotherapeutic drugs, induce apoptotic death in cancer cells as well as normal cells with high mitotic rates such as those in bone marrow and hair follicles. Preliminary studies show semi-purified preparations termed "P factor" (Pf) can block apoptosis in vitro and attenuate hair loss when applied topically in a rat model of chemotherapy-induced alopecia. The activity of Pf is mediated by two separate components termed Pfalpha was purified and its structure determined to be an organic compound with a molecule weight of 195 D. Purified Pfalpha interacts synergistically with Pfbeta to inhibit apoptosis. Here we propose to purify Pfbeta, determine its structure, and test it in vitro in different model systems of apoptosis along with Pfalpha. These studies will determine whether further valuation of Pf in animal models is justified. If Pfalpha and Pfbeta prove effective, long-range studies will evaluate their potential use in other forms of alopecia and possible other diseases associated with inappropriate apoptosis. PROPOSED COMMERCIAL APPLICATION: Currently, there are no effective means to prevent cancer therapy-induced hair loss. The development of a topically applied drug that would prevent apoptosis of scalp hair follicle cells induced by chemotherapy or irradiation would benefit many cancer patients.